This is a continuation application to study the structure and function of the low affinity receptor for IgE (FceRII/CD23). A soluble chimeric CD23 that is predicted to form a trimeric molecule similar to membrane CD23 has been produced and shown to interact in a dual manner with IgE. This molecule has a modified leucine zipper at the amino terminus (Iz-CD23). The capacity of Iz-CD23 to induce inflammatory mediator release and to interact with cell surface ligands will be determined. In addition, the current studies have indicated two strategies to improve the capacity of CD23 to control IgE-mediated activities: increase the stability of the stalk region and inhibit the cell surface proteolysis. Both aspects are part of the renewal application. As studies have indicated that the current chimera becomes increasingly unstable at 37 degrees C, additional studies to further stabilize the molecule are presented and the newly produced chimeric molecules will also be examined for both inhibition of binding of IgE to the FceRI, inflammatory mediator release and influence on B cell activation, especially IgE production. These studies will be performed both in vitro and in vivo using transgenic animals. A number of studies have indicated that induction of increased cell surface CD23 results in inhibition of IgE synthesis in both mouse and human models. An antibody that blocks CD23 degradation will be produced in order to inhibit the cell surface degradation that classically occurs. The capacity of this antibody to inhibit IgE production in both IgE high and low responder mice will be compared. In addition, the mechanism via which cross-linking CD23 in an Fc dependent manner influences CD40 induced cell proliferation will be examined. Finally, the current grant period has indicated that mouse CD23b is produced in intestinal epithelial cells and the parameters regulating this expression will be explored.